Three projects address the exchange of substances across microcirculatory barriers. One of these focuses on inflammatory stimuli and biochemical mechanisms associated with the regulation of microvascular permeability. Another addresses the role of the interstitial space in modulating lung fluid exchange and edema. The third investigates the endothelial cell and factors which promote endothelial cell injury. Two projects investigate the effects of alteration in diet upon the microcirculation. The first will address the role of a high carbohydrate, high fiber diet in protecting against human diabetic microangiopathic disorders. The second focuses on whether polyunsaturated fatty acids improve capillary blood flow and reduce platelet-endothelial cell adherence in both humans and animal models. Five projects investigate the role of the nervous system in the regulation of arteriolar vascular smooth muscle tone. 1) Studies will be made on reflex neural control of the microcirculation during hemodynamic stresses induced by pregnancy. 2) Investigations will be made on the role of alterations in brainstem integrating sites on the development and maintenance of hypertension. 3) Frequency and burst neural stimulation procedures and the role of non-adrenergic mediators will be used to address vascular smooth muscle responsiveness in the development and maintenance of hypertension. 4) The role of alpha -adrenergic subtypes in the regulation of arteriolar vascular smooth muscle tone will be investigated. 5) Studies of the role of both direct and reflex neural control of microcirculatory cutaneous blood flow during thermal and non-thermal stresses. The final project addresses angiogenic factors which promote myocardial microcirculatory neovascularization. The eleven projects are supported by three cores (Administration, Electron Microscopy & Biostatistics). There is an extraordinarily high degree of interaction among the various investigators. The investigations are directed at defining basic mechanisms involved in the physiology and pathophysiology of the microcirculation with a first step toward extending basic concepts into a clinical setting.